The goal of this project is to synthesize and test various foscarnet based pro-drugs. Although foscarnet is a potent inhibitor of HIV reverse transcriptase, its highly anionic nature leads to poor penetration into cells and additionally renders the drug unavailable for oral administration (foscarnet is administered iv). Previous studies from our laboratory showed that triesters were potential pro-drugs; unfortunately, the hydrolysis kinetics were unfavorable. Hydrolysis of the first phosphate ester was too rapid and hydrolysis of the second phosphate ester was too slow; the carboxylic acid was hydrolyzed subsequent to the first phosphate hydrolysis but prior to the second phosphate hydrolysis. Additional pro-drug strategies, based on assisted hydrolysis at phosphorus are being evaluated. Several attempts to prepare the target compounds were not successful; however, alternate synthetic strategies are now being pursued.